Project Summary/Abstract Progress against Alzheimer's disease and related dementias (ADRD) has been frustratingly slow, but effective treatments may be on the horizon. Given the scale of ADRD and its costs, even modest efficacy in delaying progression could have substantial social benefits. However, the scale of the ADRD problem also presents a financing challenge. How can we afford new therapies for large numbers of ADRD patients and those who are pre-symptomatic? This problem is exacerbated by the likelihood that clinical benefits will vary with disease stage, genotype, or other unknown factors. Payers are reluctant to pay high prices per dose for therapies, especially when these benefits may accumulate much later in life. We will bring together experts in economics, neuroscience, and ADRD care to identify and quantify alternative reimbursement strategies that ensure better access. First, using a variant of the RAND/UCLA appropriateness methods, we will identify the most promising ADRD interventions, quantify their likelihood of success and expected clinical benefit, and assess whether these benefits are likely to vary across patient subgroups. Second, we will map clinical trial endpoints used in the current ADRD pipeline to broader quality-of-life outcomes ? e.g., functional status, disease incidence, and mortality risk ? that can be used to estimate societal consequences. Third, drawing on economic theory and the exitant literature, we will develop novel reimbursement mechanisms for ADRD therapies and characterize how they would be structured. Fourth, we will adapt the Future Elderly Model (FEM), a well-validated microsimulation model, to study the long-term health and economic consequences of new ADRD technologies, and to study how these consequences would vary with different pricing mechanisms. We will study both average outcomes and changes in disparities across ADRD patients for alternative technology and pricing scenarios. Fifth, we will use the microsimulation model to study impacts of technologies and pricing scenarios on the health and economic outcomes of informal caregivers for ADRD patients. Finally, we will convene a workshop to disseminate our findings to key marketplace and policy stakeholders, and to generate discussion about potential next steps. Together, the proposed research will develop and evaluate innovative strategies to ensure that current and future ADRD patients gain access to novel therapies.